Cytokine, Head and Neck Cancer
Conditions
Brief summary
The ROMCOR study will be interested in the impact and the role of oncostatin M (OSM), a cytokine belonging to IL-6 superfamily, in the physiopathology of head and neck squamous cell carcinoma. The study team will study the impact of the presence of OSM and its main receptor OSM-R2 on several survival outcomes (overall survival, progression free survival) by multiple technics such as immunohistochemistry, transcriptomic in situ assays and spatial transcriptomic. Furthermore, the study team will try to show a link between serum level of several cytokines and in situ tumoral OSM.
Interventions
OTHERBiopsies and Blood collection
Each participant will have 2 additionnal biopsies during his/her diagnostic endoscopy plus two blood test during his/her inclusion
Sponsors
Poitiers University Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* over 18 years of age; * with suspected squamous cell carcinoma of the oral cavity, oropharynx or pharyngolarynx (any stage); * with healthy, untreated contralateral mucosa and no contraindications to biopsy; * with no history of any type of cancer; * with a WHO performance status index of 0 to 2 inclusive ; * able to receive treatment according to current European Society of Medical Oncology guidelines ; * without guardianship, curatorship or subordination; * benefiting from a Social Security scheme or benefiting from one through a third party; * have given informed consent to participate in the study.
Exclusion criteria
* previously pre-treated in the ear, nose, throat sphere by radiotherapy or having already received anti-cancer chemotherapy; * on long-term immunosuppressive therapy, defined as taking an immunosuppresseur, identified as such in the ATC classification, for 7 days, cortico-therapy \> 7.5mg/day for more than 3 months, treatment or history of anti-CD20 treatment within the year, or regular plasmatic exchange or gamma globulin infusion; * benefiting from enhanced protection, i.e. minors, persons deprived of their liberty by a judicial or administrative decision, persons staying in a health or social establishment, adults under legal protection; * pregnant or breast-feeding women of childbearing age (menopause must be documented and more than 2 years old) who refuse or do not have an effective method of contraception (hormonal/mechanical: oral, injectable, transcutaneous, implantable, intrauterine device, or surgical: tubal ligation, hysterectomy, total oophorectomy) for the duration of the study. * final diagnosis of non-squamous cell carcinoma
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To analyze the relative expression of OSM, several inflammatory cytokines and their receptors in head and neck squamous cell carcinomas (SCC). | 1 month | The relative expression of transcripts for OSM, OSM-R, as well as the main inflammatory cytokines and their receptors (LIFR, Gp130, IL-31, IL6, IL-1β, TNF-α, IL-4, IL-10, IL-34, CXCL8, CXCL2, IL-17 and GCSF) will be compared between tumor and non-tumor biopsy samples. These comparisons will also be stratified by disease stage (localized, locally advanced, metastatic). Cytokine expression will be studied by RT-qPCR after RNA extraction and retro-transcription on frozen tissue biopsies (tumor and non-tumor) in nitrogen, and the value will be expressed in relation to the expression of two common housekeeping genes, GADPH and Actin B. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Relative expression by RT-qPCR of epithelial-mesenchymal transition (EMT) transcripts will be compared in tumoral mucosa versus normal mucosa of patients | 1 month | Investigators will study the following genes : SNAI1, SERPIN B3, TGM2, ZEB1, YAP-1, FAT-1, CK13, VIM, OCT-4, SOX-2, CD-44, BMI-1 and KLF-4 |
| Correlation between relative expression of OSM and OSM-R by RT-qPCR and the relative expression of epithelial-mesenchymal transition transcripts in tumoral mucosa | 1 month | Investigators will study the following genes : SNAI1, SERPIN B3, TGM2, ZEB1, YAP-1, FAT-1, CK13, VIM, OCT-4, SOX-2, CD-44, BMI-1 and KLF-4 |
| Caracterisation of the prognostic impact of tissue-level immunohistochemistry expression of OSM and OSM-R at diagnosis on progression-free survival. | 18 month | Tissues will be classified as OSM positive (positive staining) or negative (no staining) and OSM-R positive or negative. Progression-free survival of positive and negative patients will be compared. PFS will be defined as a composite criterion :progression of the mesurable target \> 20%, progression \> 20% AND at least 5mm and emergence of new lesions PFS will be mesured at 12 and 18 months |
| Analysis of the tumor immune cell microenvironment that secret OSM in head and neck squamous cell carcinoma with the cell-selectine RNA sequencing method. | 1 month | To know what type of cells secrete OSM in the microenvironment, we will use GeoMx Nanostring (c) technique. It consists of a selective RNA or protein sequecing of immunofluorescence labelled cells on parrafine embedded tissues. Investigators will then label OSM-secreting cells with anti-OSM fluorochrome and collect it to be sequenced |
| Correlation between serum concentrations of OSM and several circulating inflammatory cytokines and their respective expression in tumor tissue in head and neck squamous cell carcinoma at diagnosis. | 1 month | OSM and other cytokines (LIFR, le Gp130, l'IL-31, l'IL6, l'IL-1β, le TNF-α, l'IL-4, l'IL-10, l'IL-34, le CXCL8, le CXCL2, l'IL-17 et le GCSF) will be analysed by the semi-quantitative ELISA technique on patients's sera. Same cytokines will be assessed in tumoral mucosa by RT-qPCR. Comparison between their relative expression by RT-qPCR and their serum concentration will be study |
| Caracterisation of the prognostic impact of serum OSM concentrations at diagnosis on progression-free survival | 1 month | Patients will be classified as high serum concentration of OSM at baseline or low serum concentration at baseline (concentration cut-off not known in literature) using the semi-quantitative ELISA technique. Progression-free survival of overexpressing and underexpressing patients will be compared. PFS will be defined as a composite criterion :progression of the mesurable target \> 20%, progression \> 20% AND at least 5mm and emergence of new lesions PFS will be mesured at 12 and 18 months |
| Caracterisation of the relationship between changes in serum cytokine concentrations (between the time of diagnosis and 3 months after the end of initial treatment) and early response to treatment (3 months after the end of initial treatment). | 18 month | For each cytokines dosed in serum, we will describe if the variation of their concentrations (R= T0 - (T0+Dt/T0))\*100 ) as an impact on the response at 3 month (defined as the V2 visit). Reponse rate is defined as (RECIST v1.1) : complete response : no residual disease is clinically or radiologically assessable at 3 month partial response : decrease of the mesurable targets of more than 30% but still assessable stable disease : modification of the mesurable targets between a decrease of less than 30% and a progression of less than 20% progression : progression of the mesurable targets of more than 20% |
| Caracterisation of the prognostic impact of transcriptomic expression of OSM and OSM-R at diagnosis on progression-free survival. | 18 month | Biopsies will be classified as OSM / OSM-R overexpressing tissue (ratio : relative expression of OSM and OSM-R in tumoral mucosa / relative expression of OSM and OSM-R in normal mucosa by RT-qPCR is above the median) or underexpressing tissue (ratio under the median). Progression-free survival of overexpressing and underexpressing patients will be compared. PFS will be defined as a composite criterion :progression of the mesurable target \> 20%, progression \> 20% AND at least 5mm and emergence of new lesions PFS will be mesured at 12 and 18 months |
Contacts
Primary ContactBAINAUD MATTHIEU, Dr
Outcome results
None listed